Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Zotepine for Behavioural and Psychological Symptoms in Dementia

An Open-Label Study

  • 50 Accesses

  • 10 Citations

Abstract

Objective: To provide initial information on the safety and efficacy of the atypical antipsychotic zotepine in the treatment of behavioural and psychological symptoms of dementia (BPSD).

Methods: This was an open-label, single-centre field study. Twenty-four patients with BPSD associated with Alzheimer’s disease (n = 12) or other forms of dementia (n = 12) were included. During the 8-week observation period, the patients received zotepine (Nipolept®) [12.5–150 mg/day] for the psychotic components of BPSD; no other treatment interventions for BPSD were allowed. At baseline, day 28 and day 56, patients were evaluated using the Clinical Global Impressions (CGI) scale; the Mini-Mental State Examination (MMSE), the Syndrome Brief Test (SKT) and the Age Concentration Test (AKT) to assess cognition; and the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfield Agitation Inventory (CMAI) to assess BPSD. General adverse effects and, more specifically, the emergence of extrapyramidal symptoms were also assessed.

Results: There was no change from baseline to day 56 in the CGI score and the caregiver burden (as indcated by the caregiver-related section of the NPI). There was also no change in cognition (as assessed by the MMSE, SKT and AKT). The neuropsychiatric symptom score according to part 1 of the NPI (especially key psychotic symptoms, aggression and disinhibition) and the CMAI scores improved by 36% and 15%, respectively, between baseline and the end of the study in a highly statistically significant fashion.

No significant differences in treatment response or adverse effect profile were noted between the 12 patients with Alzheimer’s disease and the 12 patients with other types of dementia.

Zotepine was well tolerated, with tiredness and sedation (five and four cases, respectively) being the most frequent complaints. No clinically significant emergence of extrapyramidal symptoms was seen.

Conclusions: Zotepine appears to be well tolerated and effective in treating BPSD, consistent with the performance of other atypical antipsychotic drugs in this condition. Larger, controlled studies are warranted.

This is a preview of subscription content, log in to check access.

Table I
Fig. 1

Notes

  1. 1.

    The use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. 1.

    Finkel S. Introduction to behavioural and psychological symptoms of dementia (BPSD). Int J Geriatr Psychiatry 2000; 15: S2–4

  2. 2.

    Margallo-Lana M, Swann A, O’Brien J, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatr Psychiatry 2001; 16: 39–44

  3. 3.

    Rainer M, Mucke HA, Masching A, et al. Non-cognitive symptom profiles in dementia: experience from psychiatric services and memory clinics. Psychiatr Prax 1999; 26: 71–5

  4. 4.

    Rojas-Fernandez CH, Lanctot KL, Allen DD, et al. Pharmacotherapy of behavioral and psychological symptoms of dementia: time for a different paradigm? Pharmacotherapy 2001; 21: 74–102

  5. 5.

    Jeste DV, Finkel SI. Psychosis of Alzheimer’s disease and related dementias: diagnostic criteria for a distinct syndrome. Am J Geriatr Psychiatry 2000; 8: 29–34

  6. 6.

    Lopez OL, Wisniewski SR, Becker JT, et al. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol 1999; 56: 1266–72

  7. 7.

    Ballard C, Gray A, Ayre G. Psychotic symptoms, aggression and restlessness in dementia. Rev Neurol (Paris) 1999; 155Suppl. 4: S44–52

  8. 8.

    Caligiuri MR, Jeste DV, Lacro JP. Antipsychotic-induced movement disorders in the elderly: epidemiology and treatment recommendations. Drugs Aging 2000; 17: 363–84

  9. 9.

    Masand PS. Side effects of antipsychotics in the elderly. J Clin Psychiatry 2000; 61 Suppl. 8: 43–9

  10. 10.

    Needham PL, Atkinson J, Skill MJ, et al. Zotepine: preclinical tests predict antipsychotic efficacy and an atypical profile. Psychopharmacol Bull 1996; 32: 123–8

  11. 11.

    Tatsumi M, Jansen K, Blakely RD, et al. Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol 1999; 368: 277–83

  12. 12.

    Kanba S, Yagi G, Oguchi E, et al. Neuropharmacology of zotepine, an antimanic drug: a potent blocker of D2 and 5-HT2 receptors of human brain. Jpn J Psychiatry Neurol 1991; 45: 133–4

  13. 13.

    Petit M, Raniwalla J, Tweed J, et al. A comparison of an atypical and typical antipsychotic, zotepine versus haloperidol in patients with acute exacerbation of schizophrenia: a parallel-group double-blind trial. Psychopharmacol Bull 1996; 32: 81–7

  14. 14.

    Fleischhacker WW, Barnas C, Stuppack CH, et al. Zotepine vs haloperidol in paranoid schizophrenia: a double-blind trial. Psychopharmacol Bull 1989; 25: 97–100

  15. 15.

    Sarai K, Okada M. Comparison of efficacy of zotepine and thiothixene in schizophrenia in a double-blind study. Pharmacopsychiatry 1987; 20: 38–46

  16. 16.

    Fleischhacker WW, Barnas C, Stuppack C, et al. Zotepine in the treatment of negative symptoms in chronic schizophrenia. Pharmacopsychiatry 1987; 20: 58–60

  17. 17.

    Barnas C, Stuppack CH, Miller C, et al. Zotepine in the treatment of schizophrenic patients with prevailingly negative symptoms: a double-blind trial vs haloperidol. Int Clin Psychopharmacol 1992; 7: 23–7

  18. 18.

    Kasper S, Quiner S, Barnas C, et al. Zotepine in the treatment of acute hospitalized schizophrenic episodes. Int Clin Psychopharmacol 2001; 16: 163–8

  19. 19.

    Meyer-Lindenberg A, Gruppe H, Bauer U, et al. Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study. Pharmacopsychiatry 1997; 30: 35–42

  20. 20.

    Harada T, Otsuki S. Antimanic effect of zotepine. Clin Ther 1986; 8: 406–14

  21. 21.

    McKhann G, Drachman DA, Folstein MF, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimers’s Disease. Neurology 1985; 34: 939–44

  22. 22.

    Folstein MF, Folstein S, McHugh R. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98

  23. 23.

    Cummings JL. The neuropsychiatric inventory: assessing psychopathology in patients with dementia. Neurology 1997; 48: S10–6

  24. 24.

    Lehfeld H, Erzigkeit H. The SKT: a short cognitive performance test for assessing deficits of memory and attention. Int Psychogeriatr 1997; 9: 115–21

  25. 25.

    Gatterer G, Fischer P, Simanyi M, et al. The A-K-T (‘Alters-Konzentrations-Test’) a new psychometric test for geriatric patients. Funct Neurol 1989; 4: 273–6

  26. 26.

    Koss E, Weiner M, Ernesto C, et al. Assessing patterns of agitation in Alzheimer’s disease patients with the Cohen-Mansfield Agitation Inventory. Alzheimer Dis Assoc Disord 1997; 11: 45–50

  27. 27.

    Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 212: 11–9

  28. 28.

    Chui HC, Lyness SA, Sobel E, et al. Extrapyramidal signs and psychiatric symptoms predict faster cognitive decline in Alzheimer’s disease. Arch Neurol 1994; 51: 676–81

  29. 29.

    Tune LE, Steele C, Cooper T. Neuroleptic drugs in the management of behavioral symptoms of Alzheimer’s disease. Psychiatr Clin North Am 1991; 14: 353–73

  30. 30.

    McShane R, Keene J, Gedling K, et al. Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. BMJ 1997; 314: 266–70

  31. 31.

    McKeith I, Fairbairn A, Perry R, et al. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 1992; 305: 673–8

  32. 32.

    Devanand DP, Levy SR. Neuroleptic treatment of agitation and psychosis in dementia. J Geriatr Psychiatry Neurol 1995; 8: S18–27

  33. 33.

    Ballard C, Grace J, McKeith I, et al. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer’s disease. Lancet 1998; 351: 1032–3

  34. 34.

    Devanand DP, Marder K, Michaels KS, et al. A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer’s disease. Am J Psychiatry 1998; 155: 1512–20

  35. 35.

    Devanand DP, Sackeim HA, Brown RP, et al. A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer’s disease. Arch Neurol 1989; 46: 854–7

  36. 36.

    Coccaro EF, Kramer E, Zemishlany Z, et al. Pharmacologic treatment of noncognitive behavioral disturbances in elderly demented patients. Am J Psychiatry 1990; 147: 1640–5

  37. 37.

    Allain H, Dautzenberg PH, Maurer K, et al. Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. Psychopharmacology (Berl) 2000; 148: 361–6

  38. 38.

    Kirchner V, Kelly CA, Harvey RJ. Thioridazine for dementia. Cochrane Database Syst Rev 2000; (2): CD000464 2000

  39. 39.

    De Deyn PP, Katz IR. Control of aggression and agitation in patients with dementia: efficacy and safety of risperidone. Int J Geriatr Psychiatry 2000; 15Suppl. 1: S14–22

  40. 40.

    De Deyn PP, Rabhera K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53(5): 946–55

  41. 41.

    Katz IR, Jeste DV, Mintzer JE, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial: Risperidone Study Group. J Clin Psychiatry 1999; 60(2): 107–15

  42. 42.

    Brodaty H, Ames D, Snowdon J, et al. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003; 64(2): 134–43

  43. 43.

    Clark WS, Street JS, Feldman PD, et al. The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer’s disease. J Clin Psychiatry 2001; 62: 34–40

  44. 44.

    Walker Z, Grace J, Overshot R, et al. Olanzapine in dementia with Lewy bodies: a clinical study. Int J Geriatr Psychiatry 1999; 14: 459–66

  45. 45.

    Tariot PN, Ismail MS. Use of quetiapine in elderly patients. J Clin Psychiatry 2002; 63 Suppl. 13: 21-6

Download references

Acknowledgements

This study was supported by an unconditional research grant from EBEWE Pharma Ges.m.b.H, A-4866 Unterach, Austria. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Correspondence to Dr Michael K. Rtainer.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rtainer, M.K., Mucke, H.A.M., Krüger-Rainer, C. et al. Zotepine for Behavioural and Psychological Symptoms in Dementia. CNS Drugs 18, 49–55 (2004). https://doi.org/10.2165/00023210-200418010-00005

Download citation

Keywords

  • Dementia
  • Antipsychotic Drug
  • Zolpidem
  • Clinical Global Impression
  • Extrapyramidal Symptom